For the ADP-A2M4 SPEAR T-cell product co-expressing IL-7, IL-15, dnTGF-B, and/or PDE7, previously, it has been shown that IL-15 alone could produce a small population of (stem central) memory cells, but combination with IL-7 should increase these numbers [1,2]. Thus, those two phenotypes have the potential to provide superior clinical outcomes [3,4].
A dnTGF-B receptor would help to improve the cytotoxic function of CD8+ T-cells [5,6], and reduce Treg conversion in CD4+ [7] caused by the cytokine [8].
As for PDE7, overexpression would confer resistance to the inhibitory effects of prostaglandin E2 (antigen-specific TCR downregulation) [9].